(GBV-C) is a single-stranded RNA virus that is the closest known relative of hepatitis C virus (HCV). GBV-C has not been associated with any human disease to date. However, several studies have reported a beneficial effect of GBV-C viremia on HIV disease progression - reduced HIV RNA levels, increased CD4 cell counts, and slower disease progression - predominantly in cohorts with a high proportion of men. However, the prevalence of GBV-C differs significantly between men and women, and no large prospective studies have examined the effects of GBV-C co-infection on HIV disease progression in women. In a preliminary study, we found that GBV-C genotype 2 was associated with higher CD4 cell counts compared to genotype 1, and that GBV-C genotype 2 was more sensitive to clearance after interferon treatment than GBV-C genotype 1. Therefore, we propose to evaluate the presence of GBV-C co-infection and the role of GBV-C genotype in modulating HIV disease progression in a well-characterized cohort of women with HIV/AIDS to enhance our knowledge of GBV-C/HIV interactions. This work is significant and innovative because no large prospective studies of the role of GBV-C co-infection in modulating HIV disease have been reported in HIV positive women and because its addresses a potentially beneficial interaction between GBV-C and HIV that could be exploited in the future to develop novel therapeutic strategies. PUBLIC HEALTH RELEVANCE: To date, GB virus type C (GBV-C) has not been associated with any human disease, although several studies have reported a beneficial effect of GBV-C infection on HIV disease progression. The prevalence of GBV-C may differ by gender;however, the adventitious role of GBV-C co-infection on HIV disease, as well as the potential modulatory effects of GBV-C genotype, has not yet been evaluated in a longitudinal manner in women. Such studies could ultimately lead to novel therapeutic strategies to treat HIV disease, particularly among difficult-to-treat populations and/or individuals with limited access to antiretroviral therapy.